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R Djukanovic

Publications and source records attributed to R Djukanovic.

At least 37 records · Page 2Linked to original sources
PubMed2000

Bronchial angiogenesis in severe glucocorticoid-dependent asthma.

To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects. Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E- and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4. By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and P-selectin nor in numbers of LFA-1+ and VLA-4+ cells. The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.

Adolescent↗
PubMed2000

Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation.

The authors have investigated whether the steroid-sparing effect of methotrexate (MTX) in severe orally glucocorticoid-insensitive asthmatics may be accounted for by the ability of this drug to increase the T-cell responsiveness sensitivity to dexamethasone in vitro. In addition the authors have investigated whether low-dose MTX treatment is associated with anti-inflammatory effects in peripheral blood and the bronchial mucosa. In eight patients with severe atopic asthma, using > or =15 mg x day(-1) prednisolone, the inhibitory effect of dexamethasone on mitogen stimulated peripheral blood mononuclear cells (PBMC) in vitro was tested before and after 8 weeks of uncontrolled treatment with MTX. Endobronchial biopsies were taken before and after MTX therapy in seven subsequent patients, and analysed using immunohistochemistry. In eight patients, serum was drawn for measuring levels of free interleukin (IL)-8. The in vitro sensitivity of PBMC to dexamethasone (at 1.6 x 10(-9) and 3.2 x 10(-10) mol x L(-1)) was significantly lower in the asthmatics before treatment when compared with the control subjects (p=0.03 and =0.001) but increased significantly after MTX treatment (p=0.04 and =0.02) to normal responsiveness. This was not associated with a decrease in peripheral blood T-cell numbers or activation. Except for a significant increase in the numbers of CD3+ (p=0.04), no significant numerical changes in activated T-cells, eosinophils, or mast cells were found (p>0.05). However, MTX treatment was associated with a significant fall in serum levels of free IL-8 (p=0.03). It is hypothesized that the steroid-sparing effect of methotrexate originates from increased sensitivity of lymphocytes to the inhibitory effects of glucocorticoids. The absence of an inhibitory effect on inflammatory cells in blood and mucosa suggests that this effect is achieved by modulating cell function rather than cell number.

Adolescent↗
PubMed2000

The role of co-stimulation in airway inflammation.

There is considerable evidence to support an important role for co-stimulatory molecules in regulating the proliferation and activation of T cells in the immune response. Of particular relevance is the interaction between CD28 on T cells and B7 expressed on the surface of antigen presenting cells (APCs). CTLA-4, another molecule present on activated T cells may downregulate T cell activity, but its role remains uncertain. CTLA4-Ig, a fusion protein consisting of the extracellular domain of CTLA4 and the Fc portion of human immunoglobulin G1 (IgG1), has been useful for studying the role of CD28/B7 interactions in immune responses. A number of studies have shown that CTLA4-Ig can switch off T cell activation. In an ovalbumin sensitive murine model of asthma, CTLA4-Ig treatment suppressed the response to inhaled allergen (increased airway hyperresponsiveness [AHR], IgE production, recruitment of eosinophils into the lungs, production of IL-4, IL-5, and IL-10 and increased IFNgamma production from CD3-TCR-activated T cells). Anti B7-2 treatment has similar effects suggesting that interaction of B7-2 with CD28 is important in the development of a Th-2 type inflammatory response in mice. Recent observations have been of relevance to human allergic disease. In vitro studies have shown that CTLA4-Ig or anti-B7-2 antibody can inhibit allergen-induced proliferation and cytokine production by peripheral blood mononuclear cells from atopic subjects. The role of co-stimulation has been studied in a human bronchial explant model of asthma. CTLA4-Ig fusion protein effectively blocked allergen-induced production of IL-5 and IL-13 in bronchial explants from atopic asthmatics. These studies confirm the requirement for interaction between co-stimulatory molecules in cytokine production and allergic inflammation, and point to the CD28-B7 pathway as being important to the allergen-induced inflammation in asthma. Studies of organ transplantation in primates suggest that CTLA4-Ig is extremely effective in preventing organ rejection. While phase 1 clinical trials have shown CTLA-4-Ig treatment of patients with psoriasis vulgaris to be well tolerated and to result in clinical improvement, its role in asthma management merits further investigation.

Abatacept↗
PubMed2000

Altered airway surfactant phospholipid composition and reduced lung function in asthma.

Pulmonary surfactant in bronchoalveolar lavage fluid (BALF) and induced sputum from adults with stable asthma (n = 36) and healthy controls (n = 12) was analyzed for phospholipid and protein compositions and function. Asthmatic subjects were graded as mild, moderate, or severe. Phospholipid compositions of BALF and sputum from control subjects were similar and characteristic of surfactant. For asthmatic subjects, the proportion of dipalmitoyl phosphatidylcholine (16:0/16:0PC), the major phospholipid in surfactant, decreased in sputum (P < 0.05) but not in BALF. In BALF, mole percent 16:0/16:0PC correlated with surfactant function measured in a capillary surfactometer, and sputum mole percent 16:0/16:0PC correlated with lung function (forced expiratory volume in 1 s). Neither surfactant protein A nor total protein concentration in either BALF or sputum was altered in asthma. These results suggest altered phospholipid composition and function of airway (sputum) but not alveolar (BALF) surfactant in stable asthma. Such underlying surfactant dysfunction may predispose asthmatic subjects to further surfactant inhibition by proteins or aeroallergens in acute asthma episodes and contribute to airway closure in asthma. Consequently, administration of an appropriate therapeutic surfactant could provide clinical benefit in asthma.

Adolescent↗
PubMed2000

Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness.

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.

Adolescent↗
PubMed1999

Bronchial eosinophilic infiltration in Crohn's disease in the absence of pulmonary disease.

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. METHODS: Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. RESULTS: When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. CONCLUSIONS: Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability.

Adult↗
PubMed1999

Analysis of immunoglobulin E VH transcripts in a bronchial biopsy of an asthmatic patient confirms bias towards VH5, and indicates local clonal expansion, somatic mutation and isotype switch events.

Immunoglobulin E (IgE)-dependent mechanisms play a pivotal role in mediating allergic disease. Previously, VH-Cepsilon transcripts from blood or spleen of atopic asthmatics have been analysed for VH gene usage and patterns of somatic mutation. An over-representation of the minor VH5 family has been observed, consistent with a superantigen drive. As local mucosal events in IgE production may be more significant in the disease process, we have analysed VH-Cepsilon transcripts from a bronchial biopsy of a patient with severe asthma. VH5 predominance was confirmed with 10 of 30 unique clones derived from this family. Repeated sequences, some with intraclonal variation, revealed clonal expansion and continuing mutational activity at the site. Unexpectedly, three unmutated VH-Cepsilon sequences were found, indicating that isotype switching to IgE can occur without mutation. Detection of a sister clone with extensive mutations was again consistent with local mutational activity. Evidence for local isotype switching was obtained by identification of clonally related immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin E (IgE) sequences. However, in contrast to findings in blood, no IgG4 transcripts clonally related to IgE were detected, suggesting that the balance between synthesis of IgG4 and IgE may differ between systemic and local sites. These data confirm a VH5 bias in IgE, and support the concept that IgE-synthesizing B cells arise via local differentiation.

Adult↗
PubMed1999

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma.

We have shown in nocturnal asthma that alveolar tissue eosinophils are increased at night as compared with the proximal airway, and that they correlate with the overnight decrement in lung function. As the CD4+ cell is thought to be the principal orchestrating cell in eosinophil recruitment, we evaluated its presence in the proximal and distal airways in nocturnal asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and at 4:00 A.M. separated by 1 wk. Immunohistochemical staining and morphometric analysis were used to determine the number of CD3+, CD4+, and CD8+ cells and EG2+ eosinophils per mm2 in the epithelium, lamina propria, and alveolar tissue. At 4:00 A.M., the NA group had a significantly greater number of CD4+ cells in the alveolar tissue than the NNA group (9.8 cells/ mm2 [5.6-30.8, interquartile (IQ)] versus 1.5 cells/mm2 [0-6. 3, IQ], p = 0.04). Within the NA group, there were significantly greater numbers of CD3+, CD4+, CD8+, and EG2+ cells in the proximal airway lamina propria than in the distal airway at both 4:00 P.M. and 4:00 A.M. There were no differences within the epithelium between the groups at either time point. Only alveolar tissue, not airway tissue, CD4+ cells correlated inversely with the percentage predicted FEV1 at 4:00 A.M. (r = -0.68, p = 0.0018) and positively with the number of alveolar tissue EG2+ cells (r = 0.66, p = 0.01). These findings suggest that the CD4+ lymphocyte is increased in the alveolar tissue at night in nocturnal asthma as compared with non-nocturnal asthma.

Adult↗
PubMed1999

B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation.

Asthma is a complex disorder characterized by airway hyperreactivity and inflammation. To analyze cellular interactions required for the secretion of cytokines by the bronchial mucosa, we have evaluated the ex vivo response of tissue explants to allergen. Endobronchial mucosal biopsy tissue from mild atopic asthmatic subjects and normal control subjects were maintained in culture for 24 h. To detect reactivity to allergen, the explants were stimulated with dust mite extract Dermatophagoides pteronyssinus (Der p). Our analysis revealed that without any overt stimulation, mRNA transcripts for interleukin (IL)-5 and IL-13 were expressed by asthmatic but not normal bronchial tissue. In contrast, the expression of interferon-gamma was observed in a higher proportion of cultured bronchial biopsies from the normal control subjects than in those from asthmatic subjects. Addition of Der p allergen did not change the cytokine profile of the explants from control volunteers but augmented the expression of IL-5 mRNA and induced secretion of the protein by the asthmatic bronchial tissue. In most cases, allergen also increased the production of IL-13 by bronchial tissue from asthmatic subjects. The allergen-induced secretion of IL-5 and IL-13 was inhibited by the fusion protein CTLA-4Ig, reflecting a requirement for CD80 (B7-1) and/or CD86 (B7-2) costimulation for the expression of the Th2 cytokines. This requirement for B7/CD28 costimulation is consistent with the hypothesis that IL-5 and IL-13 are produced by allergen-specific T cells resident in the asthmatic bronchial mucosa.

Adult↗
PubMed1999

The effect of processing on inflammatory markers in induced sputum.

The effects of the mucolytic agent, dithioerythritol (DTE), and the temperature at which sputum processing is conducted on cellular and biochemical markers in induced sputum was assessed. Samples from healthy and atopic asthmatic subjects were treated with either DTE or phosphate-buffered saline (PBS) at 22 or 37 degrees C and compared for cell counts and concentrations of histamine, tryptase, eosinophil cationic protein (ECP), free interleukin (IL)-8, immunoglobulin (Ig)A, IL-8/IgA complexes and secretory component (SC). In addition, the influence of DTE on in vitro mediator release from blood eosinophils, basophils and bronchoalveolar lavage (BAL) mast cells was studied. Processing with DTE improved cytospin quality and increased the cell yield and measurable ECP, tryptase, IgA and SC, but reduced levels of histamine in PBS-treated samples and had no effect on IL-8. Cell counts or mediator levels were similar when sputum was processed at 22 or 37 degrees C, even though DTE induced blood basophils and BAL mast cells to release histamine at 37 degrees C. In spiking experiments, recovery of added ECP, tryptase, total IL-8 and histamine from sputum was similar in DTE- and PBS-processed sputum, but reduced for free IL-8 in PBS-treated samples. In conclusion, dithioerythritol improves cell and mediator recovery without causing cell activation when sputum processing is conducted at room temperature. The extent of recovery depends on the mediator studied.

Asthma↗
PubMed1999

Mucosal inflammation in severe glucocorticoid-dependent asthma.

To improve our understanding of the inflammatory mechanisms underlying severe disease, a biopsy study was performed comparing 15 clinically unstable glucocorticoid-dependent asthmatics, 10 mild asthmatics, and 10 control subjects. Compared with mild asthma, severe asthma was characterized by reduced mucosal eosinophilia. Whilst no significant differences were found in the numbers of mast cells, neutrophils, CD3+ and CD4+ T-cells between the three groups, up to a 4-fold increase In the numbers of activated T-lymphocytes bearing the interleukin (IL)-2 receptor (IL-2R) was found in the mucosa in severe asthma compared to mild asthma (p = 0.03) and control subjects (p = 0.003). Compared to control subjects, the mucosa of severe asthmatics contained significantly (p = 0.02) higher numbers of IL-5+ cells, with no differences between mild and severe disease. In contrast, staining for the anti-IL-4 monoclonal antibody 3H4 revealed that biopsies from mild asthmatics contained more IL4+ cells than biopsies from severe asthmatics and control subjects (p = 0.0008). In the severe asthmatics, a close correlation (r(s) = 0.76, p = 0.005) was found between the numbers of IL-2R-bearing cells and the variability in peak expiratory flow. In conclusion, persistent T-cell activation is a prominent feature of severe asthma. These results also indicate that interleukin-5, and not interleukin-4, is upregulated in severe disease.

Administration, Topical↗
PubMed1998

The role of ICAM-1 on T-cells in the pathogenesis of asthma.

The capacity of inflammatory cells to adhere is critical to inflammatory responses and involves an array of adhesion molecules grouped into distinct families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much interest in view of increasing evidence that it plays a prominent role in allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of inflammatory cells to vascular endothelium, the extracellular matrix and epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell interactions. ICAM-1 on the surface of T-cells is thought to participate in signal transduction and may thus modulate several functions including activation, proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the receptor for the major group of rhinoviruses, the most important cause of acute asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least theoretically, modulate their function. We review here the role of ICAM-1 in asthma and focus more specifically on its expression on T-cells. We present evidence for a general increase in ICAM-1 expression in this disease including recent observations of enhanced expression on the surface of T-cells in the airways lumen. Whilst the implications of intercellular adhesion molecule- upregulation in asthma remain to be fully elucidated, its participation in cell trafficking and activation are being considered as a target for treatment. We present here early attempts to interfere with intercellular adhesion molecule-1 as an adhesion molecule involved in cell influx and studies aimed preventing virus-induced exacerbations of asthma in children based on the knowledge that intercellular adhesion molecule-1 is the receptor for rhinoviruses.

Antigen-Presenting Cells↗
PubMed1998

Sputum eosinophilia is more closely associated with airway responsiveness to bradykinin than methacholine in asthma.

Hyperresponsiveness of the airways to various spasmogenic stimuli is a characteristic feature of bronchial asthma. However, the association between the different stimuli to which asthmatic airways are hyperresponsive and airways inflammation is not completely understood. We have investigated the relationship between airway inflammation and airway hyperresponsiveness in asthma, as assessed by bronchoprovocation tests to methacholine and bradykinin, two well defined bronchoconstrictor agonists. Sputum induction by hypertonic saline and methacholine and bradykinin challenges were performed in 14 nonsmoking subjects with mild-to-moderate asthma. Airway responsiveness to either agonist did not correlate with sputum neutrophils, lymphocytes, and macrophages. Whilst the absolute number of eosinophilia failed to be significantly related to methacholine responsiveness (r=-0.47; p=0.09), it correlated markedly and significantly with provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (r=0.72; p<0.01). When expressed as % of total cell counts, sputum eosinophils correlated with both types of responsiveness (r=-056; p=0.04 and r=-0.76, p<0.001, respectively). Although the concentration of eosinophil cationic protein (ECP) in the sputum correlated with the absolute numbers of eosinophils (r=0.62; p<0.02), no correlation was found between ECP levels and the airway responsiveness to any of the agonists tested. In subjects with mild-to-moderate asthma, airway responsiveness to bradykinin is more strongly associated with the magnitude of eosinophilic inflammation in the airways than methacholine. This finding underlines the selectivity of diverse agonists in assessing airway hyperresponsiveness and cellular inflammation in asthma.

Adolescent↗
PubMed1997

The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.

CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases.

Adolescent↗
PubMed1997

Cultured nasal polyps from nonatopic and atopic patients release RANTES spontaneously and after stimulation with phytohemagglutinin.

BACKGROUND: Eosinophil infiltration of tissue is a hallmark of nasal polyposis in both nonatopic and atopic patients. These cells are thought to play a key role in the nasal polyp inflammatory process. OBJECTIVE: The objective of this study was to investigate whether cultured nasal polyps derived from nonatopic and atopic patients release RANTES both spontaneously and after phytohemagglutinin (PHA) stimulation. METHODS: Nasal polyps were obtained from 12 subjects (6 nonatopic and 6 atopic), cut into 2 to 3 mm large specimens, and cultured for 48 hours with or without PHA. RANTES was measured in the culture supernatant by ELISA (R&D Systems, U.K.). RESULTS: Immunoreactive RANTES was found to be present in the culture supernatant of nasal polyps derived from both nonatopic and atopic patients with no difference between the two groups (median: 3.8 vs 2.9 pg/mg/ml). On incubation with PHA, nasal polyps from both nonatopic and atopic patients released sevenfold and 11-fold greater amounts of RANTES than unstimulated samples. As determined by immunohistochemistry, RANTES was localized to the vascular endothelium in nasal polyps from both groups of patients. CONCLUSIONS: This study demonstrates that cultured nasal polyps derived from both nonatopic and atopic patients release RANTES spontaneously and after PHA stimulation. This observation and the finding that RANTES is present in nasal polyp endothelial cells suggest that this chemokine may be an important mediator of eosinophil and lymphocyte recruitment in both nonatopic and atopic nasal polyposis.

Adult↗
PubMed1997

Effects of high dose intravenous immunoglobulin in two severe corticosteroid insensitive asthmatic patients.

Preliminary observations of the clinical efficacy of intravenous immunoglobulin in two patients with severe corticosteroid insensitive asthma are reported. In both patients treatment with intravenous immunoglobulin resulted in clinical improvement and enabled a significant reduction in the dose of prednisolone. In one of the patients fibreoptic bronchoscopy with endobronchial biopsies was performed and peripheral blood was analysed by flow cytometry before and after treatment. Immunohistological analysis of the biopsy samples after treatment showed a decrease in the number of all cell types, especially CD3+ T cells, CD4+ T cells, and activated CD25+ T lymphocytes, which was associated with a reduction in peripheral blood T cell activation. Intravenous immunoglobulin may be a valid option for the treatment of corticosteroid insensitive asthma. To elucidate the role and mode of action of intravenous immunoglobulin further studies in larger groups of patients are needed.

Adolescent↗
PubMed1997

Transforming growth factor-beta 1 in asthma. Measurement in bronchoalveolar lavage fluid.

Airway wall remodeling is an established pathological feature in asthma. Its causes are not well understood, but one mediator of potential relevance is transforming growth factor-beta 1 (TGF-beta 1). We have measured levels of immunoreactive TGF-beta 1 in bronchoalveolar lavage (BAL) fluid from clinically stable atopic asthmatics and healthy control subjects. We have also examined the influence of allergen exposure on TGF-beta 1 release in the airways using a segmental bronchoprovocation model, with BAL performed at two time points following endobronchial allergen and sham saline challenges. Basal concentrations of TGF-beta 1 were significantly higher in asthmatics than control subjects (median 8.0 versus 5.5 pg/ml, p = 0.027). Following segmental bronchoprovocation, concentrations of TGF-beta 1 at the allergen- and saline-challenged sites were not significantly different after 10 min, (31.3 versus 25.0 pg/ml, p = 0.78), but after 24 h there were significantly higher TGF-beta 1 concentrations at the allergen-challenged sites (46.0 versus 21.5 pg/ml, p = 0.017). We conclude that basal TGF-beta 1 levels in the airways are elevated in atopic asthma and that these levels increase further in response to allergen exposure. These findings are consistent with the hypothesis that TGF-beta 1 is implicated in airway wall remodeling in asthma.

Adult↗